5-Azacytidine changes gene expression and causes developmental arrest of early chick embryo

Abstract

Methylation of DNA appears to be an important maintenance mechanism for inhibiting gene expression during development in vertebrates. 5-azacytidine (5-azaC) is used as an experimental tool for demethylation and it induces differentiation in various systems. In the chick embryo, the first cellular migrations signal the onset of primitive streak and gastrula formation and result in neural induction and morphogenesis of the embryonic axis. In the present work with the early chick embryo, 5-azaC perturbs normal cellular migrations and the embryos produce an atypical short, thickened primitive streak. These embryos have the tendency to form neural tissue but the embryonic axis shows sparse identity of patterning along its length. A small percentage of embryos display formation of double embryonic axes. Blastula embryos show reduced expression of some polypeptides and express characteristic polypeptides which are not present in morula embryos normally. Under the influence of 5-azaC, blastula embryos expressed all the polypeptides which are characteristic of embryos at both the morula and the blastula stages. If 5-azaC perturbs DNA methylation as the chick embryo develops from the histologically simple blastula, then the wave of methylation which has been reported to start at the late blastula and continues during postgastrulation in vertebrate embryos does not seem to be important for the induction of mesodermal and of neural tissues, but is important for the patterning of these tissues.